title: Tumor suppressor dual-specificity phosphatase 6 (DUSP6) impairs cell invasion and epithelial-mesenchymal transition (EMT)-associated phenotype.
abstract: Suppressive effects of DUSP6 in tumorigenesis and EMT-associated properties were observed. Dual-specificity phosphatase (DUSP6) is a MAP kinase phosphatase (MKP) negatively regulating the activity of ERK, one of the major molecular switches in the MAPK signaling cascade propagating the signaling responses during malignancies. The impact of DUSP6 in EMT and its contribution to tumor dissemination has not yet been characterized. Due to differences in tumor microenvironments affecting cell signaling during cancer progression, DUSP6 may play varying roles in tumor development. We sought to examine the potential role of DUSP6-mediated tumorigenesis and EMT-associated properties in two aerodigestive tract cancers, namely, esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). Significant loss of DUSP6 was observed in 100% of 11 ESCC cell lines and 71% of seven NPC cell lines. DUSP6 expression was down-regulated in 40% of 30 ESCC tumor tissues and 75% of 20 NPC tumor tissues compared to their respective normal counterparts. Suppressive effects of DUSP6 in tumor formation and cancer cell mobility are seen in in vivo tumorigenicity assay and in vitro colony formation, three-dimensional Matrigel culture, cell migration and invasion chamber tests. Notably, overexpression of DUSP6 impairs EMT-associated properties. Furthermore, tissue microarray analysis reveals a clinical association of DUSP6 expression with better patient survival. Taken together, our study provides a novel insight into understanding the functional impact of DUSP6 in tumorigenesis and metastasis of ESCC and NPC.
authors.affiliation: Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors.forename: Victor Chun Lam
authors.initials: VC
authors.lastname: Wong
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: Josephine Mun Yee
authors.initials: JM
authors.lastname: Ko
authors.forename: Kwok Wah
authors.initials: KW
authors.lastname: Chan
authors.forename: Yuen Piu
authors.initials: YP
authors.lastname: Chan
authors.forename: Simon
authors.initials: S
authors.lastname: Law
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.forename: Dora Lai-Wan
authors.initials: DL
authors.lastname: Kwong
authors.forename: Hong Lok
authors.initials: HL
authors.lastname: Lung
authors.forename: Gopesh
authors.initials: G
authors.lastname: Srivastava
authors.forename: Johnny Cheuk On
authors.initials: JC
authors.lastname: Tang
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Zabarovsky
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stanbridge
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics / Q000378:metabolism*; D057890:Epigenomics; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D012333:RNA, Messenger; C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6